Prostate cancer is the second leading cause of cancer death in the United States. The primary cause of mortality is distant metastatic disease for which androgen deprivation is the initial therapeutic standard. However, virtually all patients treated with androgen deprivation will progress in a predictable and irreversible manner to androgen independence and hormone refractory state. The wide spread use of PSA in the clinic has altered the profile of patients with hormone-refractory prostate cancer. The spectrum now encompasses patients with marked differences in disease burden and symptoms with three main categories of patients that can be identified: Non- metastatic androgen independent disease with rising PSA (i.e. PSA-only disease), rising PSA with stable metastatic disease, and increasing PSA with objective progression. Although historically the role of systemic therapy has been palliative in this stage of the disease, progress in drug development has led to investigating the impact of chemotherapy on survival. Even though it is likely that taxane-based chemotherapy may have an impact on survival, the effect nonetheless is not optimal in that it is complicated by toxicities and has doubtful curative potential. As with any metastatic cancer, the ultimate goals of therapy in this setting are clear: to prolong life, to decrease morbidity, and to increase quality of life. Therefore it is particularly important to investigate alternative novel approaches that stem from observation on the biology of the disease